Bioequivalence and Bioavailability Forum

Thanks to both of you for the feedback. It's all very enlightening.

❝ ❝ The general reason, that no reference to previous studies is allowed when it comes to widening of the acceptance range. CV_intra,ref >30% must st be demonstrated within the submitted study.

Isn't a significant chunk of the logic for conducting BE studies of non-linear PK drugs at the higher/lower strength due to this "sensitivity" to distinguish between formulation effects being the greastest at that particular strength? Doesn't that imply it is done so because the variability at the highest/lowest strength is theorectically greatest and, therefore, if one can pass BE at this dose, then BE can be implied for the other strengths? Shall I tack on another run-on sentence?

I don't mean to kick a dead horse, but I'm wondering why scientifically (irrespective of historical precedent or variability throughout the dose range--as good as these answers are) one cannot use the results from one study to design another given the drugs are the same (both test and reference). What I'm getting at here is that if one suspects a drug may be highly variable, given the current interpretation of the regulations, one has to do one of two...no, make that three things:

1. Scrap the originally planned standard BE study for the higher strength (in my case) and conduct it in replicate design.
   
2. Burst the development budget by conducting a replicate design first and then designing a standard BE study with the appropriate confidence intervals next.
   
3. Down a bottle of Schützomycin and hope the bacterial infection that set in one's scalp from all the head scratching is sensitive to this antibiotic (hopefully, a generic whose BE to the reference product was conducted in replicate design).

Does that sound about right? Can linking the results from the lower strength study to the higher strenth study be argued on scientific merit (assuming the science is correct)?